Addition of PEGPH20 to Nab-Paclitaxel/Gemcitabine in Pancreatic Ductal Adenocarcinoma

Key Points

The addition of PEGPH20 to nab-paclitaxel/gemcitabine improved progression-free survival.

The risk of thromboembolic events was reduced with the use of enoxaparin prophylaxis in all patients.

In a phase II study reported in the Journal of Clinical Oncology, Hingorani et al found that the addition of pegvorhyaluronidase alfa (PEGPH20) to nab-paclitaxel (Abraxane)/gemcitabine improved progression-free survival in patients with previously untreated metastatic pancreatic ductal adenocarcinoma. Excessive hyaluronan accumulation in the tumor microenvironment is characteristic of metastatic disease and is associated with impaired perfusion; PEGPH20 has been shown to degrade hyaluronan, potentially increasing drug delivery.

Study Details

In the trial, a total of 279 patients were randomized to receive PEGPH20 plus nab-paclitaxel/gemcitabine (n = 166) or nab-paclitaxel/gemcitabine alone (n = 113). The trial was put on hold after an early imbalance of thromboembolic events in the PEGPH20 group was observed (stage 1, March 2013 to April 2014). The trial was subsequently resumed (stage 2, August 2014 to February 2016) with a 2:1 randomization, with patients with a history of thromboembolic events or risk factors being excluded and all patients receiving enoxaparin prophylaxis. The primary endpoints were progression-free survival and thromboembolic event rate. Tumor hyaluronan levels were measured retrospectively; among 246 patients with hyaluronan data, 84 (34%) had hyaluronan-high tumors.

The most common treatment-related grade 3 or 4 adverse events with a significantly higher incidence in the PEGPH20 group included muscle spasms (13% vs 1%), neutropenia (29% vs 18%), and myalgia (5% vs 0%). During stage 1 of the trial, thromboembolic events occurred in 43% of patients in the PEGPH20 group vs 25% in the control group (P = .03). During stage 2, when patients received enoxaparin prophylaxis, thromboembolic events occurred in 14% vs 10% (P = .77).

The investigators concluded: “This study met its primary endpoints of [progression-free survival] and [thromboembolic] event rate. The largest improvement in [progression-free survival] was observed in patients with [hyaluronan]-high tumors who received [PEGPH20 plus nab-paclitaxel/gemcitabine]. A similar [thromboembolic] event rate was observed between the treatment groups in stage 2 of the trial.”